The present invention relates to pharmaceutical compositions, in particular dermatological or cosmetic, comprising hydrous lipidic lamellar phases or liposomes containing a retinoid or a structural analogue thereof such as a carotenoid.
It is well known that certain retinoids such as the tretinoin, are used in therapeutics, particularly in the treatment against acne.
Tretinoin or its homologues such as the 13-cis-retinoic acid or the etretinate are drugs which are commonly used at the present time for treating acne. The anti-acneic action of carotenoids is also known. Various galenic forms have been proposed among which the most active one is based on an alcoholic solution of tretinoin intended for local administration. In this connection, reference can be made to a medicine bearing the trade name of ABEREL.RTM.. There are various formulations of ABEREL comprising 0.025%, 0.05% and 0.1% of tretinoin. The excipient is based on ethyl alcohol at 95.degree. . The effects of tretinoin are summarized in the VIDAL dictionary, "Specialites Pharmaceutiques Francaises", notably in the edition of 1985 and more complete comments can be obtained from the article of Lorraine Kligman et al published in "The Journal of Investigative Dermatology", Volume 73, no. 5, part I, pages 354-358, issued in 1979, with an experimentation on the skin of Hairless Rhino mice which is the most suitable model for experimenting in the inhibition of comedos. In this article, Kligman stresses that tretinoin has also a positive effect to remove folds and wrinkles from the skin of the Hairless Rhino mouse.
There are also medicines intended for oral administration containing retinoids such as the 13-cis-retinoic acid or the etretinate, for treating serious acnes, psoriasis and other serious keratinisation disorders.
The main drawback of the tretinoid is, by general path, its systemic toxicity (teratogenicity, and undesirable effects due to hypervitaminosis A), and by local path, its irritant action liable to require, in some cases, the stopping of the treatment. It is emphasized in the VIDAL dictionary, that this action characterized by a dry, slightly smarting erithema, located mainly around the mouth and on the neck, is directly connected to the activity of the product but, however, this action disappears when applications are spaced out.
According to some authors, the systemic toxicity of tretinoin, even by local path, is a factor limiting its use (see antepenultimate paragraph on page 357 of the aforesaid article).
Thus, it appears that the irritant effect of tretinoin is directly linked to its activity.
Moreover, it is stated that the ABEREL.RTM. forms, as a conventional excipient, in a solution at 0.2% and 0.3%, which are strongly dosed with tretinoin, are contraindicated in acne and reserved for the treatment of keratinisation disorders.
Finally, the alcoholic solution used in the ABEREL.RTM. forms, dosed at 0.025% also proves to show an irriting effect.
In a further therapeutic application, reference can be made to the Albert Kligman U.S. Pat. No. 3,856,934 relating to a composition for the depigmentation of the skin, containing tretinoin (also called acid A vitamin or also trans-retinoic acid).
Lorraine Kligman et al further report in the review "Connective Tissue Research", 1984, volume 12, pages 139-150 that tretinoin at a 0.05% dose when applied during 5 and 10 weeks, stimulates fibroblasts and favours the reparation of the damage caused by a ultraviolet irradiation. Thus, Kligman discloses in this article that tretinoin has an activity favouring the formation of a subepidermic reconstruction area, which is considered as favorable to "rejuvenate" the epidermis.